An interdisciplinary research effort has been initiated between the Schneider peptide lab and the Pochan materials morphology lab to develop a new class of biomaterials whose structure and consequent function is responsive to environmental cues. These materials will be constructed using peptides that are a priori designed at the molecular level to self assemble into targeted nano- and microscopic structures. Significantly, by using peptides as the fundamental material building blocks one can engineer materials whose morphology will predictably change or respond to specific environmental cues. The ability to actively manipulate material morphology will lead to "smart" biomaterials whose structure and consequent function is responsive to its environment. Materials derived herein may find potential use as gating vehicles for molecular delivery, hydrogels for tissue engineering scaffolds, and as stimuli-sensitive, peptide-based nanocomposites for in vivo applications. Resulting material will be thoroughly characterized from the molecular structure in dilute solution (CD, NMR, analytical ultracentrifugation) up through the final material morphology (cryogenic transmission and scanning electron microscopy, laser scanning confocal microscopy, neutron and x-ray scattering, oscillatory shear rheology) to establish self-assembly design principles. Biocompatibility of the material structures will be interrogated with cellular assays to draw specific bioproperty-structure relationships, relationships not rigorously pursued in most current biomaterial research programs. The preparation of biologically inspired materials via molecular self-assembly is being pursued across many disciplines. Vesicular aggregates have been prepared from self-assembling peptides produced recombinantly and from glycopeptides. Synthetic peptides have been designed which self-assemble into fibrils and tapes, micelles/bundles and fibular gels. All of these examples demonstrate that peptides can be used to prepare materials. However, the structures of these materials are static. This proposal describes our efforts to design, synthesize, and characterize biomaterials whose structures, and therefore functions, can be actively controlled. The self-assembly rules and active morphological controls established here will then be used to prepare advanced biomaterials having potential use as gating vehicles for prolonged delivery of macromolecules, tissue engineering scaffolds, and as stimuli-sensitive, peptide-based nanocomposites. The first step in realizing these long range goals is to establish the rules by which material morphology can be predictably self assembled and actively controlled.